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CONCLUSIONS: Establishing an MCID is important for determining clinically relevant change in the LEAPS, both for treatment studies and for individual patients in clinical care. For clinical use, the proposed MCID is 3 points for the LEAPS total score and 2 points for the LEAPS productivity subscale score.

Cell-free DNA analysis via methylation and fragmentation profiling has advanced minimally invasive cancer detection; however, broader application has been limited by small cohorts and inconsistent data processing. Here we collated 1,074 cfMeDIP-seq profiles across 9 studies, comprising cancer samples from 11 cancer types, carriers of Li-Fraumeni syndrome and healthy controls. We developed a uniform computational workflow to mitigate technical and biological confounders across cohorts. This...

Human DNA polymerase θ (Polθ) is essential for microhomology-mediated end-joining (MMEJ) and represents a therapeutic vulnerability in homologous recombination (HR)-deficient cancers. Although reversible inhibitors of Polθ have advanced into clinical development, covalent chemical probes remain unexplored. Analysis of a previously described structure of the reversible inhibitor compound 37 bound to Polθ identified Cys2411 as an accessible residue 7.4 Å adjacent to the inhibitor binding site....

Antimicrobial resistance is driven by inappropriate use of antibiotics for acute respiratory infections (ARIs), which is a major challenge in primary care in low- and middle-income countries. Here we conducted a pragmatic, cluster randomized controlled trial in 34 township hospitals in two rural counties of Guangdong, China, to evaluate whether a digitally enabled stewardship program could reduce antibiotic prescribing. The intervention combined training and guidelines for doctors; concise,...

Biomanufacturing can play a pivotal role in the transition away from fossil fuel dependence for the production of chemicals and fuels. There is growing interest in inexpensive alternative bioproduction feedstocks from renewable sources that avoid competing with food production for land use. Ethylene glycol, a C2 compound that can be recovered from plastic waste or derived from carbon dioxide, is gaining attention as a carbon source for microbial processes. Here, we systematically evaluate...

Fuel cells are a promising energy conversion technology with high efficiency and environmental benefits. This paper provides a concise review of recent advances in solid oxide fuel cells (SOFCs), focusing on electrode and catalyst materials. It quantitatively compares performance metrics such as power density and polarization resistance to identify optimization pathways. Key technical bottlenecks-particularly durability and high cost-are critically analyzed. The study also outlines the major...

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Crassulacean acid metabolism (CAM) is a specialized photosynthetic pathway that enhances water-use efficiency by temporally separating nocturnal CO(2) uptake from daytime decarboxylation and carbon fixation. To uncover the regulatory mechanisms coordinating these temporal dynamics, we generated high-resolution, 48 h time-course transcriptomes for the CAM model Kalanchoe fedtschenkoi under both 12 h/12 h light/dark (LD) cycles and continuous light (LL). A rhythmicity analysis revealed that diel...

CONCLUSIONS: We identified a high number of treatable psychiatric illnesses in the referred parents. Partnerships between pediatric complex care teams and psychiatry services and using virtual care may help with timely and accessible mental health care for this at-risk population. Future research could investigate adherence to and efficacy of treatment recommendations for this caregiver population.

CONCLUSIONS AND RELEVANCE: Actigraphy measures of sleep phase variability and daily activity amplitude were associated with depressive relapse, supporting actigraphy as a potential scalable biomarker to identify high-risk individuals and enable timely, personalized relapse prevention in MDD.

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 postconception weeks (PCW), initially serving as a scaffold for Purkinje cells...

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brainstem tumor affecting children, with median survival under 12 months and no curative treatments. Current therapeutic development centers on ONC201, an imipridone that exhibits clinical activity by selectively activating human caseinolytic protease P (hClpP). X-ray analysis of the hClpP:ONC201 complex offers insights into optimizing the chemical structure of ONC201. Based on this, we designed and synthesized simplified piperazine-based...

Anisotropic flow and radial flow are two key probes of the expansion dynamics and properties of the quark-gluon plasma (QGP). While anisotropic flow has been extensively studied, radial flow, which governs the system's radial expansion, has received less attention. Notably, direct experimental evidence for the global and collective nature of radial flow fluctuations has been lacking. This Letter presents the first measurement of transverse momentum (p_{T}) dependence of radial flow fluctuations...

Multi-omics cancer data provides complementary views of tumorigenesis and progression. Technical challenges exist in integrating these heterogeneous data into deep learning models to better understand tumorigenesis and predict cancer recurrence. We herein propose a novel end-to-end deep learning method (MULGONET) for cancer recurrence prediction and biomarker discovery. First, MULGONET can effectively solve the curse of dimensionality and the lack of model interpretability in multi-omics data...

Captured CO(2) can either be stored or converted into a carbon-containing product. Both processes require energy to liberate CO(2) from the CO(2) capture solution. One way to bypass the energy-intensive recovery of CO(2) is to integrate CO(2) capture and conversion. For example, OH^(-)-based capture solutions react with CO(2) to form (bi)carbonate-rich liquids, which can then be electrochemically converted into upgraded carbon-containing products while regenerating OH^(-) for further CO(2)...

Single-cell RNA sequencing (scRNA-seq) enables detailed comparisons of gene expression across cells and conditions. Single-cell differential expression analysis faces challenges like sample correlation, individual variation, and scalability. We develop a fast and scalable linear mixed-effects model (LMM) estimation algorithm, FLASH-MM, to address these issues. We reformulate aspects of the linear mixed model estimation procedure to make it faster, by reducing computational complexity and memory...

Lymphedema is a chronic complication of breast cancer treatment, and early intervention is crucial to reduce morbidity. This study evaluated the role of blood-based cytokine biomarkers in the prognostication of breast cancer-related lymphedema (BCRL) to improve risk prediction. A secondary analysis of inflammatory biomarkers for BCRL was performed using a previously published cohort of 147 breast cancer patients who had undergone serum cytokine profiling during their treatment at the Princess...

Bacteria have evolved a wide array of defence systems to combat phage infection, many of which rely on complex signalling systems and large protein complexes to function¹. Here we describe a 164-residue prophage-encoded protein that defends bacteria by sensing conserved oligomeric components of phage assembly. This protein, called ring interacting pore 1 (Rip1), is activated by the portal or small terminase proteins of infecting phages-oligomeric ring-shaped complexes that are essential for...

Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O(2)), we sought to determine whether the modality of HIF-1 activation directs its function. Through...

CONCLUSIONS: DHTs are feasible and can capture clinically meaningful psychological and physiological data in high-risk pediatric and family populations with LFS. They enable timely detection of distress and facilitate targeted interventions. Our findings can inform best practices for patient-centered DHT integration into clinical care, with relevance to pediatric oncology and broader digital health contexts.